Recombinant Interleukin 1 and Tumor Necrosis Factor Acting in Synergy to Release Thromboxane, 6-KETO-PGF1α, and PGEI2, by Human Neutrophils

Abstract

The cyclooxygenase pathway promotes formation of an endoperoxide that is the precursor of prostaglandins (PG), thromboxanes (Tx) and prostacyclins (PGI2), all of which have important biologic activities. In this study, we examined the ability of human polymorphonuclears (PMN) to synthesize TRxA2, 6-KETO-PGF1 alpha and PGE2 in response to human recombinant interleukin 1 (IL1) and tumor necrosis factor (TNF) alone and in combination. Blood was obtained from healthy donors and whole blood was centrifuged over Ficoll-Hypaque in 2% dextran for 30 min. PMNs were resuspended in Gey's buffer, exposed to the IL1 and TNF at 300 ng/ml and 0.5 ng/ml concentrations, and incubate for 30 min. at 10(6) cell/ml. Results indicate that IL1 and TNF alone have little or no effect on human neutrophils to synthesize TxA2, 6-KETO-PGF1 alpha and PGE2 production. This effect was completely inhibited by two non-steroidal anti-inflammatory drugs (i.e. indomethacin and proglumetacin).